Along this line, the decrease in pediatric non-responders may reflect the progressive loss of LARGE1-expressing neurons impacting on the amount of release of this protein from damaged/ apoptotic neurons to the CSF whereas lower base-line level in adult SMA patients classified as therapy non-responders may reflect an insufficient compensatory LARGE1-upregulation during in the molecular etiology of the disease. Here, LARGE1 is linked to proximal spinal muscular atrophy.